Epigenetic modulating compounds as potential therapeutic agents for oesophageal cancer management.

Posted on: 21 Jun 2018

 Epigenetic modulating compounds as potential therapeutic agents for oesophageal cancer management.

 

 

Principal Investigator: Dr. Órla P. Barry

Clinical Challenge being addressed:

Treatment of oesophageal cancer.

Linked Breakthrough Research Priorities: 1, 6

                                                       

Project Summary:

Despite recent advances in treatment strategies for oesophageal cancer, there has been no significant improvement in overall survival rate for advanced disease. Thus, new strategies are necessary to improve treatment options for patients with oesophageal cancer.

Epigenetics is a relatively new field of molecular biology. It is a complex mechanism of gene regulation, defined as the collection of heritable changes on DNA that affects the packaging of chromatin. Epigenetic changes are different from mutations that change the underlying structure of DNA and has a normal and vital process in cell differentiation and development. In general, however, cancer (including oesophageal cancer) is a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. Changes in DNA methylation patterns are known to be key drivers of oesophageal carcinogenesis.

Approach:

Epigenetic treatment has been approved by regulatory agencies for treatment of non-solid tumours such as leukemias, lymphomas and myeloma. The success achieved in clinical responses of such tumours suggests that similar results might be achieved in solid tumours such as oesophageal tumours. In our study we will use FDA approved epigenetic drugs alone and in combination with standard anticancer therapies to see if these drugs can alter some key hallmarks of cancer i.e. cancer cell growth, migration and increased sensitivity to existing cytotoxic drugs. We will focus particularly on oesophageal cancer that currently does not respond well to anticancer drugs. It is our desire that epigenetic therapy may be identified as an effective and in the future well-tolerated treatment for oesophageal cancer.

 

 

Selected Relevant References:

Hypermethylation of MAPK13 Promoter in Oesophageal Squamous Cell Carcinoma Is Associated with Loss of p38δ MAPK Expression. O' Callaghan C, Fanning LJ, Barry OP. Cancers (Basel). 2015 Oct 23;7(4):2124-33.

 

 p38δ MAPK phenotype: an indicator of chemotherapeutic response in oesophageal squamous cell carcinoma. O'Callaghan C, Fanning LJ, Barry OP. Anticancer Drugs. 2015 Jan;26(1):46-55.

 

 Loss of p38δ mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth. O'Callaghan C, Fanning LJ, Houston A, Barry OP. Int J Oncol. 2013 Aug;43(2):405-15.

 

p38δ MAPK: Emerging Roles of a Neglected Isoform. O'Callaghan C, Fanning LJ, Barry OP.

Int J Cell Biol, 2014;2014:272689. Review.

 

 

© Site Designed by Granite Digital